Abstract
Members of the Kruppel-like factor (KLF) family have been considered as the tumor suppressors for their inhibitory effects on cell proliferation. Dysregulation of KLF2, a member of KLF family, has been observed in various cancer types. However, its expression pattern and functions in the pancreatic ductal adenocarcinoma (PDAC) are unknown. In this study, we examined the expression of KLF2 in PDAC clinical samples and evaluated the functions of KLF2 in the progression of PDAC. KLF2 is shown to be downregulated in PDAC clinical samples and overexpression of KLF2 inhibits the growth, migration, and metastasis of PDAC cancer cells. KLF2 interacts with beta-catenin and negatively regulates the beta-catenin/TCF signaling. Taken together, this study suggests the suppressive functions of KLF2 in PDAC.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5–29.
Kumaran S, Samantha KS, Halagowder D. Does beta-catenin cross-regulate NFkappaB signalling in pancreatic cancer and chronic pancreatitis? Pathobiology. 2015;82:28–35.
Xu W, Wang Z, Zhang W, et al. Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/beta-catenin signaling pathway. Cancer Lett. 2015;356:613–27.
Chiurillo MA. Role of the WNT/beta-catenin pathway in gastric cancer. An in-depth literature review. World J Exp Med. 2015;5:84–102.
Buttar NS, Fernandez-Zapico ME, Urrutia R. Key role of kruppel-like factor proteins in pancreatic cancer and other gastrointestinal neoplasias. Curr Opin Gastroenterol. 2006;22:505–11.
Turner J, Crossley M. Basic kruppel-like factor functions within a network of interacting haematopoietic transcription factors. Int J Biochem Cell Biol. 1999;31:1169–74.
Gao Y, Ding Y, Chen H, Chen H, Zhou J. Targeting kruppel-like factor 5 (KLF5) for cancer therapy. Curr Top Med Chem. 2015;15:699–713.
Lahiri SK, Zhao J. Kruppel-like factor 8 emerges as an important regulator of cancer. Am J Transl Res. 2012;4:357–63.
DiFeo A, Narla G, Martignetti JA. Emerging roles of kruppel-like factor 6 and kruppel-like factor 6 splice variant 1 in ovarian cancer progression and treatment. Mt Sinai J Med. 2009;76:557–66. New York.
Duhagon MA, Hurt EM, Sotelo-Silveira JR, Zhang X, Farrar WL. Genomic profiling of tumor initiating prostatospheres. BMC Genomics. 2010;11:324.
Wang F, Zhu Y, Huang Y, et al. Transcriptional repression of WEE1 by kruppel-like factor 2 is involved in DNA damage-induced apoptosis. Oncogene. 2005;24:3875–85.
Nie FQ, Sun M, Yang JS, et al. Long noncoding rna anril promotes non-small cell lung cancer cell proliferation and inhibits apoptosis by silencing KLF2 and p21 expression. Mol Cancer Ther. 2015;14:268–77.
Xie P, Tang Y, Shen S, et al. Smurf1 ubiquitin ligase targets kruppel-like factor KLF2 for ubiquitination and degradation in human lung cancer H1299 cells. Biochem Biophys Res Commun. 2011;407:254–9.
Xu TP, Liu XX, Xia R, et al. SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene (E pubmed ahead of print). 2015.
Xia R, Jin FY, Lu K, et al. Suz12 promotes gastric cancer cell proliferation and metastasis by regulating KLF2 and e-cadherin. Tumour Biol (E pubmed ahead of print). 2015.
Yin L, Wang JP, Xu TP, et al. Downregulation of kruppel-like factor 2 is associated with poor prognosis for nonsmall-cell lung cancer. Tumour Biol. 2015;36:3075–84.
Taniguchi H, Jacinto FV, Villanueva A, et al. Silencing of kruppel-like factor 2 by the histone methyltransferase ezh2 in human cancer. Oncogene. 2012;31:1988–94.
Wei Y, Chen G, You L, Zhao Y. Krupel-like factor 8 is a potential prognostic factor for pancreatic cancer. Chin Med J. 2014;127:856–9.
Chakroborty D, Sarkar C, Yu H, et al. Dopamine stabilizes tumor blood vessels by up-regulating angiopoietin 1 expression in pericytes and kruppel-like factor-2 expression in tumor endothelial cells. Proc Natl Acad Sci U S A. 2011;108:20730–5.
Qiao F, Yao F, Chen L, et al. Kruppel-like factor 9 was down-regulated in esophageal squamous cell carcinoma and negatively regulated beta-catenin/TCF signaling. Molecular carcinogenesis (E pubmed ahead of print). 2015.
Evans PM, Chen X, Zhang W, Liu C. KLF4 interacts with beta-catenin/TCF4 and blocks p300/CBP recruitment by beta-catenin. Mol Cell Biol. 2010;30:372–81.
Zhang W, Chen X, Kato Y, et al. Novel cross talk of kruppel-like factor 4 and beta-catenin regulates normal intestinal homeostasis and tumor repression. Mol Cell Biol. 2006;26:2055–64.
Acknowledgments
This work was supported by the findings from the National Natural Science Foundation of China (81272728), Shanghai municipal commission of health and family planning (201440338), Shanghai Minhang district commission of science and technology (2014 MW22), and Shanghai Minhang district commission of Science and Technology (2011MHZ06, 2011MHZ25).
Conflicts of interest
None
Author information
Authors and Affiliations
Corresponding authors
Additional information
Dexiang Zhang and Yuedi Dai contributed equally to this work.
Rights and permissions
About this article
Cite this article
Zhang, D., Dai, Y., Cai, Y. et al. KLF2 is downregulated in pancreatic ductal adenocarcinoma and inhibits the growth and migration of cancer cells. Tumor Biol. 37, 3425–3431 (2016). https://doi.org/10.1007/s13277-015-4053-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13277-015-4053-3